Open AccessInhibition of NF-κB Activity Enhances Sensitivity to Anticancer Drugs in Cholangiocarcinoma Cells
Author(s) -
Wunchana Seubwai,
Kulthida Vaeteewoottacharn,
Ratthaphol Kraiklang,
Kazuo Umezawa,
Seiji Okada,
Sopit Wongkham
Publication year - 2016
Publication title -
oncology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 57
eISSN - 1555-3906
pISSN - 0965-0407
DOI - 10.3727/096504015x14424348426071
Subject(s) - doxorubicin , cisplatin , cancer research , apoptosis , multiple drug resistance , efflux , atp binding cassette transporter , cancer cell , pharmacology , viability assay , multidrug resistance associated protein 2 , drug resistance , cancer , chemotherapy , drug , nf κb , biology , transporter , biochemistry , gene , genetics , microbiology and biotechnology
Cholangiocarcinoma (CCA) is a dismal cancer. At present, there is no effective chemotherapeutic regimen for CCA. This may be due to the marked resistance of CCA to chemotherapy drugs, for which a mechanism remains unknown. Nuclear factor-κB (NF-κB) is constitutively activated in a variety of cancer cells, including CCA. It has been shown to play roles in growth, metastasis, and chemoresistance of cancer. In the present study, we examined whether NF-κB is involved in the chemoresistance of CCA and whether dehydroxymethylepoxyquinomicin (DHMEQ), an effective NF-κB inhibitor, can overcome the drug resistance of CCA. Two CCA cell lines, KKU-M213 and KKU-M214, were treated with DHMEQ and/or chemotherapeutic drugs. Cell viability, apoptosis, and the expressions of the ATP-binding cassette (ABC) transporters were compared. The combination of chemotherapy drugs, 5-fluorouracil, cisplatin, and doxorubicin, with DHMEQ significantly enhanced the cytotoxicity of all chemotherapeutic drugs compared to DHMEQ or drug alone. Furthermore, the mRNA level of ABCB1, a multidrug-resistant protein, was significantly decreased in the 5-fluorouracil combined with DHMEQ-treated cells. These findings suggest that the inhibition of NF-κB by DHMEQ enhanced the chemoresponsiveness of CCA cells, possibly by reducing the expression of ABC transporter. Inhibition of NF-κB may be a potential chemodrug-sensitizing strategy for chemoresistant cancer such as CCA.